title: Association of phosphorylated serine/arginine (SR) splicing factors with the U1-small ribonucleoprotein (snRNP) autoantigen complex accompanies apoptotic cell death.
abstract: Proteins subject to proteolysis or phosphorylation during apoptosis are commonly precipitated by autoantibodies found in the serum of patients with systemic lupus erythematosus (SLE). We screened a panel of murine monoclonal and human monospecific sera reactive with known autoantigens for their ability to selectively precipitate phosphoproteins from apoptotic Jurkat T cell lysates. Sera known to recognize the U1-small nuclear ribonucleoprotein (snRNP) complex (confirmed by their ability to precipitate U1-snRNA) selectively precipitated a phosphoprotein complex (pp54, pp42, pp34, and pp23) from apoptotic lysates. Monoclonal antibodies reactive with U1-snRNP proteins precipitated the same phosphoprotein complex from apoptotic lysates. The phosphorylation and/or recruitment of these proteins to the U1-snRNP complex is induced by multiple apoptotic stimuli (e.g., Fas ligation, gamma irradiation, or UV irradiation), and is blocked by overexpression of bcl-2. The U1-snRNP-associated phosphoprotein complex is immunoprecipitated by monoclonal antibodies reactive with serine/arginine (SR) proteins that comprise a structurally related family of splicing factors. The association of phosphorylated SR proteins with the U1-snRNP complex in cells undergoing apoptosis suggests a mechanism for regulation of alternative splicing of apoptotic effector molecules.
authors.affiliation: Department of Medicine, Division of Rheumatology, Immunology, and Allergy, Brigham & Women's Hospital, Boston, Massachusetts 02115, USA.
authors.forename: P J
authors.initials: PJ
authors.lastname: Utz
authors.forename: M
authors.initials: M
authors.lastname: Hottelet
authors.forename: W J
authors.initials: WJ
authors.lastname: van Venrooij
authors.forename: P
authors.initials: P
authors.lastname: Anderson
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D006801:Humans; D007106:Immune Sera / Q000276:immunology; D019169:Jurkat Cells; D046911:Macromolecular Substances; D051379:Mice; D009687:Nuclear Proteins / Q000276:immunology*; D010750:Phosphoproteins / Q000276:immunology*; D012326:RNA Splicing / Q000276:immunology; D012342:RNA, Small Nuclear / Q000276:immunology; D016601:RNA-Binding Proteins / Q000276:immunology*; D017412:Ribonucleoprotein, U1 Small Nuclear / Q000276:immunology*; D012261:Ribonucleoproteins; D000068103:Serine-Arginine Splicing Factors; D017381:Spliceosomes / Q000276:immunology; D019014:fas Receptor / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D001324:Autoantigens; D007106:Immune Sera; D046911:Macromolecular Substances; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012342:RNA, Small Nuclear; D016601:RNA-Binding Proteins; D017412:Ribonucleoprotein, U1 Small Nuclear; D012261:Ribonucleoproteins; C499372:SRSF2 protein, mouse; D019014:fas Receptor; C073288:SRSF2 protein, human; D000068103:Serine-Arginine Splicing Factors